OP0249 IS PREVENTION BETTER THAN CURE? DATA FROM A MONOCENTRIC RANDOMIZED CLINICAL TRIAL TO PREVENT ACUTE PHASE REACTION RELATED TO INTRAVENOUS BISPHOSPHONATES
Authors: R. DI Taranto, C. Crotti, A. Amati, F. Zucchi, R. Caporali, M. Varenna
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Acute phase reaction (APR) is a transient flu-like syndrome with fever, chills, fatigue, malaise, and musculoskeletal symptoms, often occurring 24-36 hours after intravenous bisphosphonates (IV-BPs) administration and usually resolving within 2-3 days[1]. Avoiding APR could increase patients' compliance to treatment and reduce patients' discomfort. <h3>Objectives</h3> In this monocentric, randomized, open-label, parallel-group study, we examined the efficacy of low dose of 6metilprednisone (6MP), paracetamol (PAR) or placebo (PBO) in reducing the incidence of APR. <h3>Methods</h3> We prospectively enrolled patients from March 2022 to December 2022. Patients were randomly allocated to PAR 1000 mg BID for 3 days, 6MP 4 mg BID for 3 days or PBO after IV-BPs (zoledronate (ZOL) 5 mg or neridronate (NER) 100 mg). A scale ranging from 0=absence, 1=mild, 2=moderate, and 3=severe was used to rate symptoms. Arthromyalgia (AM) included arthralgia, myalgia, arthritis, and chest pain; systemic symptoms (SS) included headache, nausea, fatigue, fever, and Health Assessment Questionnaire (HAQ). AM, CS, fever and HAQ were assessed at baseline and at day 4. APR was defined as the worsening of &gt;2 points in AM, CS score, fever (&gt;37.5°), and/or the worsening of 22% or increase of 0.25 in HAQ score[2]. Comparisons were performed by T test and chi-square test. Logistic regression was used to analyze protective and predictive factors for APR occurrence. All patients have signed informed consent. <h3>Results</h3> Ninety-five patients were enrolled: mean age±standard deviation (SD) was 57.0±14.6 yrs, mean BMI±SD was 24.51±4.1, 69.5% females, 70.5% menopausal women, 10.5% had previous exposure to oral BPs. Fourteen patients were under chronic treatment with statins. Patients were treated with BPs for osteoporosis (n=16; 17%), Paget's disease of bone (n=5; 5%) and complex regional pain syndrome type 1 (n=74; 78%). 29 patients were allocated in 6MP arm, 29 in the PAR arm and 37 in the PBO arm. The incidence rates of AM and SS in ZOL were 46.7% and 60%, respectively. The incidence rate of AM and SS in NER were 38.8% and 21.4%, respectively. 6MP prophylaxis significantly reduced the incidence of AM (p=0.03) and HAQ worsening of 22% or increase of 0.25 (p=0.01 and p=0.05, respectively), but did not prevent the incidence of SS (p=0.23). PAR and PBO did not modify the incidence of AM, SS, and worsening of HAQ. Chronic use of statins prevented incidence of AM and worsening of HAQ (p=0.029 and p=0.015, respectively) but did not impact SS score. Previous therapy with oral BPs did not prevent APR. Among protective variables for the incidence of AM were recognized older age (OR 0,95, CI 1.01-1.11, p=0.02) and 6MP prophylaxis (OR 5.0, CI 1.79-22.97, p=0.03). Concomitant statins, previous exposure to oral BPs, 25OH vitamin D3 (25OHD3) serum levels or 25OHD3 ongoing supplementation did not prevent APR. Higher BMI (OR 1.32, CI 1.07-1.65, p=0.01) and treatment with ZOL (OR 31.6, CI 2.3-431.96, p=0.01) were predictive factors for the occurrence of fever. <h3>Conclusion</h3> Our data demonstrated that low dose 6MP prophylaxis is effective in preventing the most common features of APR, compared to PAR or PBO. In contrast to literature, previous exposition to oral BPs, normal 25OHD3 serum levels or 25OHD3 supplementation did not have impact on the occurrence of APR. <h3>References</h3> [1]Olson K et al. <i>J Oncol Pharm Pract</i>. 2007 [2]Goldsmith C et al. <i>J Rheumatol</i> 1993 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.